Integrative omics analysis identifies biomarkers of idiopathic pulmonary fibrosis

• Published in: Cellular and molecular life sciences : CMLS 2022-01, Vol.79 (1), p.66, Article 66
• Main Authors: Zheng, Peiyan, Sun, Shixue, Wang, Jingxian, Cheng, Zhangkai Jason, Lei, Kuan Cheok, Xue, Mingshan, Zhang, Teng, Huang, Huimin, Zhang, Xiaohua Douglas, Sun, Baoqing
• Format: Article
• Language: English
• Subjects: Alveoli; Animals; Biochemistry; Biomarkers; Biomarkers - analysis; Biomedical and Life Sciences; Biomedicine; Bleomycin; Bleomycin - toxicity; Butyrophilin; Butyrophilins - genetics; Cell Biology; Cell differentiation; Cell Differentiation - genetics; Cell Proliferation - genetics; Differentiation (biology); Disease Models, Animal; Epithelial cells; Epithelium; Extracellular matrix; Extracellular Matrix - metabolism; Female; Fibrosis; Gene expression; Gene Expression Profiling; Genes; Humans; Idiopathic Pulmonary Fibrosis - genetics; Idiopathic Pulmonary Fibrosis - pathology; Immune system; Inflammation; Life Sciences; Lung diseases; Male; Mice; Mice, Inbred C57BL; Middle Aged; Myelin and Lymphocyte-Associated Proteolipid Proteins - genetics; Original; Original Article; Phases; Proteome - genetics; Proteomics; Pulmonary fibrosis; Repair; RNA-Seq; Transcription; Transcriptome - genetics; Transcriptomics; Wound healing; Wound Healing - genetics
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-021-04094-0

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by chronic progressive pulmonary fibrosis and a poor prognosis. Genetic studies, including transcriptomic and proteomics, have provided new insight into revealing mechanisms of IPF. Herein we provided a novel strategy to identify biomarkers by integrative analysis of transcriptomic and proteomic profiles of IPF patients. We examined the landscape of IPF patients' gene expression in the transcription and translation phases and investigated the expression and functions of two new potential biomarkers. Differentially expressed (DE) mRNAs were mainly enriched in pathways associated with immune system activities and inflammatory responses, while DE proteins are related to extracellular matrix production and wound repair. The upregulated genes in both phases are associated with wound repair and cell differentiation, while the downregulated genes in both phases are associated with reduced immune activities and the damage of the alveolar tissues. On this basis, we identified thirteen potential marker genes. Among them, we validated the expression changes of butyrophilin-like 9 (BTNL9) and plasmolipin (PLLP) and investigated their functional pathways in the IPF mechanism. Both genes are downregulated in the tissues of IPF patients and Bleomycin-induced mice, and co-expression analysis indicates that they have a protective effect by inhibiting extracellular matrix production and promoting wound repair in alveolar epithelial cells.